Hallucinogenic drugs are partial agonists of the human platelet shape change response: a physiological model of the 5-HT2 receptor

• Published in: Biological psychiatry (1969) Vol. 26; no. 3; p. 297
• Main Authors: McClue, S J, Brazell, C, Stahl, S M
• Format: Journal Article
• Language: English
• Published: United States 01-07-1989
• Subjects: Blood Platelets - drug effects; Brain - drug effects; Dose-Response Relationship, Drug; Hallucinogens - pharmacology; Humans; Lysergic Acid Diethylamide - analogs & derivatives; Lysergic Acid Diethylamide - pharmacology; Platelet Aggregation - drug effects; Receptors, Serotonin - drug effects; Serotonin - pharmacology
• ISSN: 0006-3223
• DOI: 10.1016/0006-3223(89)90042-5

We have assayed several phenylalkylamine and indolealkylamine hallucinogens, as well as structurally similar nonhallucinogens, for their effect on human platelet shape change, a physiological model for the central serotonergic 5-HT2 receptor. The hallucinogenic drugs lysergic acid diethylamide (LSD-25), N,N-dimethyltryptamine (N,N-DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), 4-iodo-2,5-dimethoxyphenylisopropylamine (DOI), bufotenine, and mescaline all showed a characteristic 5-HT2 partial agonist effect on platelet shape change. Nonhallucinogens with structural similarity to hallucinogens did not share this profile. Lisuride, methysergide, and lysergic acid showed antagonism of 5-HT-induced shape change, but none were shape change agonists. Other "psychoactive" or mood-altering drugs (cocaine, amphetamine, phencyclidine) showed poor antagonism of 5-HT-induced platelet shape change. This work refines recent ideas that some of the behavioral effects of LSD-type hallucinogens in humans are due to their actions at 5-HT2 receptors and suggests that these hallucinogens are partial 5-HT2 agonists.